Institute of Clinical Medicine, National Yang Ming Chiao Tung University, 155 Li-Nong Street, Section Peitou, Taipei 112, Taiwan.
Viruses. 2023 Feb 17;15(2):559. doi: 10.3390/v15020559.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk factors, individual genetic predisposition is a major determinant of HCC risk. Familial clustering of HCC has been observed, and a hereditary factor likely contributes to the risk of HCC development. The familial aggregation may depend on a shared environment and genetic background as well as the interactions of environmental and genetic factors. Genome-wide association studies (GWASs) are one of the most practical tools for mapping the patterns of inheritance for the most common form of genomic variation, single nucleotide polymorphisms. This approach is practical for investigating genetic variants across the human genome, which is affected by thousands of common genetic variants that do not follow Mendelian inheritance. This review article summarizes the academic knowledge of GWAS-identified genetic loci and their association with HCC. We summarize the GWASs in accordance with various chronic hepatitis virus infection statuses. This genetic profiling could be used to identify candidate biomarkers to refine HCC screening and management by enabling individual risk-based personalization and stratification. A more comprehensive understanding of the genetic mechanisms underlying individual predisposition to HCC may lead to improvements in the prevention and early diagnosis of HCC and the development of effective treatment strategies.
肝细胞癌 (HCC) 是全球癌症相关死亡的主要原因之一。HCC 的危险因素包括慢性乙型和丙型肝炎病毒感染、过量饮酒、肥胖、代谢疾病和黄曲霉毒素暴露。除了这些病毒和环境危险因素外，个体遗传易感性是 HCC 风险的主要决定因素。已经观察到 HCC 的家族聚集，遗传因素可能导致 HCC 发展的风险增加。家族聚集可能取决于共同的环境和遗传背景以及环境和遗传因素的相互作用。全基因组关联研究 (GWAS) 是最实用的工具之一，用于绘制最常见的基因组变异形式——单核苷酸多态性的遗传模式。这种方法适用于研究人类基因组中的遗传变异，因为人类基因组受到数千种不遵循孟德尔遗传的常见遗传变异的影响。本文综述了 GWAS 鉴定的遗传位点及其与 HCC 的相关性的学术知识。我们根据各种慢性肝炎病毒感染状态对 GWAS 进行了总结。这种基因谱分析可以通过基于个体风险的个性化和分层，来识别候选生物标志物，以改进 HCC 的筛查和管理。更全面地了解个体易患 HCC 的遗传机制，可能会改善 HCC 的预防和早期诊断，并开发有效的治疗策略。
